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Advances in PSMA-targeted therapy for prostate cancer

Prostate Cancer and Prostatic Diseases volume 25, pages 11–26 (2022)Cite this article

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A Correction to this article was published on 06 July 2021

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Abstract

Prostate-specific membrane antigen (PSMA), a transmembrane glycoprotein located on the cell membrane, is specifically and highly expressed in prostate cancer (PCa). Besides, its expression level is related to tumor invasiveness. As a molecular target of PCa, PSMA has been extensively studied in the past two decades. Currently, a great deal of evidence suggests that significant progresses have been made in the PSMA-targeted therapy of PCa. Herein, different PSMA-targeted therapies for PCa are reviewed, including radioligand therapy (177Lu-PSMA-RLT, 225Ac-PSMA-RLT), antibody-drug conjugates (MLN2704, PSMA-MMAE, MEDI3726), cellular immunotherapy (CAR-T, CAR/NK-92, PSMA-targeted BiTE), photodynamic therapy, imaging-guided surgery (radionuclide-guided surgery, fluorescence-guided surgery, multimodal imaging-guided surgery), and ultrasound-mediated nanobubble destruction.

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Fig. 1: Tumor therapies targeting PSMA.

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References

  1. Xiang J, Yan H, Li J, Wang X, Chen H, Zheng X. Transperineal versus transrectal prostate biopsy in the diagnosis of prostate cancer: a systematic review and meta-analysis. World J Surg Oncol. 2019;17:31–41.

    Article  PubMed  PubMed Central  Google Scholar 

  2. Ingrosso G, Detti B, Scartoni D, Lancia A, Giacomelli I, Baki M, et al. Current therapeutic options in metastatic castration-resistant prostate cancer. Semin Oncol. 2018;45:303–15.

    Article  CAS  PubMed  Google Scholar 

  3. Nizialek E, Antonarakis ES. PARP inhibitors in metastatic prostate cancer: evidence to date. Cancer Manag Res. 2020;12:8105–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Jones W, Griffiths K, Barata PC, Paller CJ. PSMA review of the current status of PSMA-targeted imaging and radioligand therapy. Cancers. 2020;12:1367.

    Article  CAS  PubMed Central  Google Scholar 

  5. Czerwinska M, Bilewicz A, Kruszewski M, Wegierek-Ciuk A, Lankoff A. Targeted radionuclide therapy of prostate cancer-from basic research to clinical perspectives. Molecules. 2020;25:1743–74.

    Article  CAS  PubMed Central  Google Scholar 

  6. Kinoshita Y, Kuratsukuri K, Landas S, Imaida K, Rovito PM Jr., Wang CY, et al. Expression of prostate-specific membrane antigen in normal and malignant human tissues. World J Surg. 2006;30:628–36.

    Article  PubMed  Google Scholar 

  7. Cimadamore A, Cheng M, Santoni M, Lopez-Beltran A, Battelli N, Massari F, et al. New prostate cancer targets for diagnosis, imaging, and therapy: focus on prostate-specific membrane antigen. Front Oncol. 2018;8:653–63.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Aloysius H, Hu L. Targeted prodrug approaches for hormone refractory prostate cancer. Med Res Rev. 2015;35:554–85.

    Article  CAS  PubMed  Google Scholar 

  9. Pastorino S, Riondato M, Uccelli L, Giovacchini G, Giovannini E, Duce V, et al. Toward the discovery and development of PSMA targeted inhibitors for nuclear medicine applications. Curr Radiopharm. 2020;13:63–79.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Bander NH, Trabulsi EJ, Kostakoglu L, Yao D, Vallabhajosula S, Smith-Jones P, et al. Targeting metastatic prostate cancer with radiolabeled monoclonal antibody J591 to the extracellular domain of prostate specific membrane antigen. J Urol. 2003;170:1717–21.

    Article  CAS  PubMed  Google Scholar 

  11. Wang AZ, Farokhzad OC. Current progress of aptamer-based molecular imaging. J Nucl Med. 2014;55:353–6.

    Article  CAS  PubMed  Google Scholar 

  12. Hussain AF, Tur MK, Barth S. An aptamer-siRNA chimera silences the eukaryotic elongation factor 2 gene and induces apoptosis in cancers expressing alphavbeta3 integrin. Nucleic Acid Ther. 2013;23:203–12.

    Article  CAS  PubMed  Google Scholar 

  13. Lupold SE, Hicke BJ, Lin Y, Coffey DS. Identification and characterization of nuclease-stabilized RNA molecules that bind human prostate cancer cells via the prostate-specific membrane antigen. Cancer Res. 2002;62:4029–33.

    CAS  PubMed  Google Scholar 

  14. Dassie JP, Liu XY, Thomas GS, Whitaker RM, Thiel KW, Stockdale KR, et al. Systemic administration of optimized aptamer-siRNA chimeras promotes regression of PSMA-expressing tumors. Nat Biotechnol. 2009;27:839–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Rockey WM, Hernandez FJ, Huang SY, Cao S, Howell CA, Thomas GS, et al. Rational truncation of an RNA aptamer to prostate-specific membrane antigen using computational structural modeling. Nucleic Acid Ther. 2011;21:299–314.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Hillier SM, Maresca KP, Femia FJ, Marquis JC, Foss CA, Nguyen N, et al. Preclinical evaluation of novel glutamate-urea-lysine analogues that target prostate-specific membrane antigen as molecular imaging pharmaceuticals for prostate cancer. Cancer Res. 2009;69:6932–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Bouchelouche K, Turkbey B, Choyke PL. PSMA PET and radionuclide therapy in prostate cancer. Semin Nucl Med. 2016;46:522–35.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Baum RP, Kulkarni HR, Schuchardt C, Singh A, Wirtz M, Wiessalla S, et al. 177Lu-labeled prostate-specific membrane antigen radioligand therapy of metastatic castration-resistant prostate cancer: safety and efficacy. J Nucl Med. 2016;57:1006–13.

    Article  CAS  PubMed  Google Scholar 

  19. Ahmadzadehfar H, Rahbar K, Kurpig S, Bogemann M, Claesener M, Eppard E, et al. Early side effects and first results of radioligand therapy with (177)Lu-DKFZ-617 PSMA of castrate-resistant metastatic prostate cancer: a two-centre study. EJNMMI Res. 2015;5:114–21.

    PubMed  Google Scholar 

  20. Ahmadzadehfar H, Wegen S, Yordanova A, Fimmers R, Kurpig S, Eppard E, et al. Overall survival and response pattern of castration-resistant metastatic prostate cancer to multiple cycles of radioligand therapy using [(177)Lu]Lu-PSMA-617. Eur J Nucl Med Mol Imaging. 2017;44:1448–54.

    Article  CAS  PubMed  Google Scholar 

  21. von Eyben FE, Roviello G, Kiljunen T, Uprimny C, Virgolini I, Kairemo K, et al. Third-line treatment and (177)Lu-PSMA radioligand therapy of metastatic castration-resistant prostate cancer: a systematic review. Eur J Nucl Med Mol Imaging. 2018;45:496–508.

    Article  CAS  Google Scholar 

  22. Gillessen S, de Bono JS, Sartor O, Omlin AG Reply to Finn E. von Eyben, Irene Virgolini and Giandomenico Roviello’s Letter to the Editor re: Silke Gillessen, Gerhardt Attard, Tomasz M. Beer, et al. Management of patients with advanced prostate cancer: the report of the advanced prostate cancer consensus conference APCCC 2017. Eur Urol 2018;73:178–211.

  23. Hofman MS, Violet J, Hicks RJ, Ferdinandus J, Thang SP, Akhurst T, et al. [177 Lu]-PSMA-617 radionuclide treatment in patients with metastatic castration-resistant prostate cancer (LuPSMA trial): a single-centre, single-arm, phase 2 study. Lancet Oncol. 2018;19:825–33.

    Article  CAS  PubMed  Google Scholar 

  24. Violet J, Sandhu S, Iravani A, Ferdinandus J, Thang SP, Kong G, et al. Long-term follow-up and outcomes of retreatment in an expanded 50-patient single-center phase II prospective trial of (177)Lu-PSMA-617 theranostics in metastatic castration-resistant prostate cancer. J Nucl Med. 2020;61:857–65.

    Article  PubMed  PubMed Central  Google Scholar 

  25. Yadav MP, Ballal S, Bal C, Sahoo RK, Damle NA, Tripathi M, et al. Efficacy and safety of 177Lu-PSMA-617 radioligand therapy in metastatic castration-resistant prostate cancer patients. Clin Nucl Med. 2020;45:19–31.

    Article  PubMed  Google Scholar 

  26. Gillessen S, Attard G, Beer TM, Beltran H, Bjartell A, Bossi A, et al. Management of patients with advanced prostate cancer: report of the advanced prostate cancer consensus conference 2019. Eur Urol. 2020;77:508–47.

    Article  CAS  PubMed  Google Scholar 

  27. Hofman MS, Emmett L, Sandhu S, Iravani A, Joshua AM, Goh JC, et al. [177Lu]Lu-PSMA-617 versus cabazitaxel in patients with metastatic castration-resistant prostate cancer (TheraP): a randomised, open-label, phase 2 trial. Lancet. 2021;397:797–804.

    Article  CAS  PubMed  Google Scholar 

  28. Sathekge M, Bruchertseifer F, Vorster M, Lawal IO, Knoesen O, Mahapane J, et al. Predictors of overall and disease-free survival in metastatic castration-resistant prostate cancer patients receiving (225)Ac-PSMA-617 radioligand therapy. J Nucl Med. 2020;61:62–9.

    Article  CAS  PubMed  Google Scholar 

  29. Navalkissoor S, Grossman A. Targeted alpha particle therapy for neuroendocrine tumours: the next generation of peptide receptor radionuclide therapy. Neuroendocrinology. 2019;108:256–64.

    Article  CAS  PubMed  Google Scholar 

  30. Kratochwil C, Bruchertseifer F, Giesel FL, Weis M, Verburg FA, Mottaghy F, et al. 225Ac-PSMA-617 for PSMA-targeted alpha-radiation therapy of metastatic castration-resistant prostate cancer. J Nucl Med. 2016;57:1941–4.

    Article  CAS  PubMed  Google Scholar 

  31. Yadav MP, Ballal S, Sahoo RK, Tripathi M, Seth A, Bal C. Efficacy and safety of (225)Ac-PSMA-617 targeted alpha therapy in metastatic castration-resistant prostate cancer patients. Theranostics. 2020;10:9364–77.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Kratochwil C, Bruchertseifer F, Rathke H, Hohenfellner M, Giesel FL, Haberkorn U, et al. Targeted alpha-therapy of metastatic castration-resistant prostate cancer with (225)Ac-PSMA-617: swimmer-plot analysis suggests efficacy regarding duration of tumor control. J Nucl Med. 2018;59:795–802.

    Article  CAS  PubMed  Google Scholar 

  33. Agrawal S. The role of 225Ac-PSMA-617 in chemotherapy-naive patients with advanced prostate cancer: Is it the new beginning. Indian J Urol. 2020;36:69–70.

    Article  PubMed  PubMed Central  Google Scholar 

  34. Khreish F, Ebert N, Ries M, Maus S, Rosar F, Bohnenberger H, et al. (225)Ac-PSMA-617/(177)Lu-PSMA-617 tandem therapy of metastatic castration-resistant prostate cancer: pilot experience. Eur J Nucl Med Mol Imaging. 2020;47:721–8.

    Article  CAS  PubMed  Google Scholar 

  35. Zhu ML, Horbinski CM, Garzotto M, Qian DZ, Beer TM, Kyprianou N. Tubulin-targeting chemotherapy impairs androgen receptor activity in prostate cancer. Cancer Res. 2010;70:7992–8002.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Basher MA, Rahman KM, Jackson PJM, Thurston DE, Fox KR. Sequence-selective binding of C8-conjugated pyrrolobenzodiazepines (PBDs) to DNA. Biophys Chem. 2017;230:53–61.

    Article  CAS  PubMed  Google Scholar 

  37. Galsky MD, Eisenberger M, Moore-Cooper S, Kelly WK, Slovin SF, DeLaCruz A, et al. Phase I trial of the prostate-specific membrane antigen-directed immunoconjugate MLN2704 in patients with progressive metastatic castration-resistant prostate cancer. J Clin Oncol. 2008;26:2147–54.

    Article  CAS  PubMed  Google Scholar 

  38. Milowsky MI, Galsky MD, Morris MJ, Crona DJ, George DJ, Dreicer R, et al. Phase 1/2 multiple ascending dose trial of the prostate-specific membrane antigen-targeted antibody drug conjugate MLN2704 in metastatic castration-resistant prostate cancer. Urol Oncol. 2016;34:e15–21.

    Article  CAS  Google Scholar 

  39. DiPippo VA, Olson WC, Nguyen HM, Brown LG, Vessella RL, Corey E. Efficacy studies of an antibody-drug conjugate PSMA-ADC in patient-derived prostate cancer xenografts. Prostate. 2015;75:303–13.

    Article  CAS  PubMed  Google Scholar 

  40. Murga JD, Moorji SM, Han AQ, Magargal WW, DiPippo VA, Olson WC. Synergistic co-targeting of prostate-specific membrane antigen and androgen receptor in prostate cancer. Prostate. 2015;75:242–54.

    Article  CAS  PubMed  Google Scholar 

  41. DiPippo VA, Nguyen HM, Brown LG, Olson WC, Vessella RL, Corey E. Addition of PSMA ADC to enzalutamide therapy significantly improves survival in in vivo model of castration resistant prostate cancer. Prostate. 2016;76:325–34.

    Article  CAS  PubMed  Google Scholar 

  42. Dangshe Ma, Hopf CE, Malewicz AD. Potent antitumor activity of an auristatin-conjugated, fully human monoclonal antibody to prostate-specific membrane antigen. Clin Cancer Res. 2006;12:2591–6.

  43. Petrylak DP, Kantoff P, Vogelzang NJ, Mega A, Fleming MT, Stephenson JJ Jr., et al. Phase 1 study of PSMA ADC, an antibody-drug conjugate targeting prostate-specific membrane antigen, in chemotherapy-refractory prostate cancer. Prostate. 2019;79:604–13.

    Article  CAS  PubMed  Google Scholar 

  44. Petrylak DP, Vogelzang NJ, Chatta K, Fleming MT, Smith DC, Appleman LJ, et al. PSMA ADC monotherapy in patients with progressive metastatic castration-resistant prostate cancer following abiraterone and/or enzalutamide: efficacy and safety in open-label single-arm phase 2 study. Prostate. 2020;80:99–108.

    Article  CAS  PubMed  Google Scholar 

  45. Ryan CJ, Smith MR, de Bono JS, Molina A, Logothetis CJ, de Souza P, et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N Engl J Med. 2013;368:138–48.

    Article  CAS  PubMed  Google Scholar 

  46. Scher HI, Fizazi K, Saad F, Taplin ME, Sternberg CN, Miller K, et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med. 2012;367:1187–97.

    Article  CAS  PubMed  Google Scholar 

  47. Cho S, Zammarchi F, Williams DG, Havenith CEG, Monks NR, Tyrer P, et al. Antitumor activity of MEDI3726 (ADCT-401), a pyrrolobenzodiazepine antibody-drug conjugate targeting PSMA, in preclinical models of prostate cancer. Mol Cancer Ther. 2018;17:2176–86.

    Article  CAS  PubMed  Google Scholar 

  48. Hinrichs MJM, Ryan PM, Zheng B, Afif-Rider S, Yu XQ, Gunsior M, et al. Fractionated dosing improves preclinical therapeutic index of pyrrolobenzodiazepine-containing antibody drug conjugates. Clin Cancer Res. 2017;23:5858–68.

    Article  CAS  PubMed  Google Scholar 

  49. Bono JSD, Fleming MT, Wang JS-Z, Cathomas R, Williams M, Bothos JG, et al. MEDI3726, a prostate-specific membrane antigen (PSMA)-targeted antibody-drug conjugate (ADC) in mCRPC after failure of abiraterone or enzalutamide. J Clin Oncol. 2020;38:99.

    Article  Google Scholar 

  50. Titov A, Valiullina A, Zmievskaya E, Zaikova E, Petukhov A, Miftakhova R, et al. Advancing CAR T-cell therapy for solid tumors: lessons learned from lymphoma treatment. Cancers 2020;12:125–46.

    Article  CAS  PubMed Central  Google Scholar 

  51. Ma Q, Safar M, Holmes E, Wang Y, Boynton AL, Junghans RP. Anti-prostate specific membrane antigen designer T cells for prostate cancer therapy. Prostate. 2004;61:12–25.

    Article  CAS  PubMed  Google Scholar 

  52. Ma Q, Gomes EM, Lo AS, Junghans RP. Advanced generation anti-prostate specific membrane antigen designer T cells for prostate cancer immunotherapy. Prostate. 2014;74:286–96.

    Article  CAS  PubMed  Google Scholar 

  53. Xie F, Ling L, van Dam H, Zhou F, Zhang L. TGF-beta signaling in cancer metastasis. Acta Biochim Biophys Sin. 2018;50:121–32.

    Article  CAS  PubMed  Google Scholar 

  54. Kloss CC, Lee J, Zhang A, Chen F, Melenhorst JJ, Lacey SF, et al. Dominant-negative TGF-beta receptor enhances PSMA-targeted human CAR T cell proliferation and augments prostate cancer eradication. Mol Ther. 2018;26:1855–66.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Junghans RP, Ma Q, Rathore R, Gomes EM, Bais AJ, Lo AS, et al. Phase I trial of anti-PSMA designer CAR-T cells in prostate cancer: possible role for interacting interleukin 2-T cell pharmacodynamics as a determinant of clinical response. Prostate. 2016;76:1257–70.

    Article  CAS  PubMed  Google Scholar 

  56. Bonifant CL, Jackson HJ, Brentjens RJ, Curran KJ. Toxicity and management in CAR T-cell therapy. Mol Ther Oncolytic. 2016;3:16011–7.

    Article  CAS  Google Scholar 

  57. Chen X, Han J, Chu J, Zhang L, Zhang J, Chen C, et al. A combinational therapy of EGFR-CAR NK cells and oncolytic herpes simplex virus 1 for breast cancer brain metastases. Oncotarget. 2016;7:27764–77.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Genssler S, Burger MC, Zhang C, Oelsner S, Mildenberger I, Wagner M, et al. Dual targeting of glioblastoma with chimeric antigen receptor-engineered natural killer cells overcomes heterogeneity of target antigen expression and enhances antitumor activity and survival. Oncoimmunology. 2016;5:e1119354–66.

    Article  CAS  PubMed  Google Scholar 

  59. Tonn T, Schwabe D, Klingemann HG, Becker S, Esser R, Koehl U, et al. Treatment of patients with advanced cancer with the natural killer cell line NK-92. Cytotherapy. 2013;15:1563–70.

    Article  CAS  PubMed  Google Scholar 

  60. Williams BA, Law AD, Routy B, denHollander N, Gupta V, Wang X-H, et al. A phase I trial of NK-92 cells for refractory hematological malignancies relapsing after autologous hematopoietic cell transplantation shows safety and evidence of efficacy. Oncotarget. 2017;8:89256–68.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Klingemann H, Boissel L, Toneguzzo F. Natural killer cells for immunotherapy - advantages of the NK-92 cell line over blood NK cells. Front Immunol. 2016;7:91–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Zhang C, Oberoi P, Oelsner S, Waldmann A, Lindner A, Tonn T, et al. Chimeric antigen receptor-engineered NK-92 cells: an off-the-shelf cellular therapeutic for targeted elimination of cancer cells and induction of protective antitumor immunity. Front Immunol. 2017;8:533–49.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Montagner IM, Penna A, Fracasso G, Carpanese D, Dalla Pieta A, Barbieri V, et al. Anti-PSMA CAR-engineered NK-92 cells: an off-the-shelf cell therapy for prostate cancer. Cells. 2020;9:1382–97.

    Article  CAS  PubMed Central  Google Scholar 

  64. Einsele H, Borghaei H, Orlowski RZ, Subklewe M, Roboz GJ, Zugmaier G, et al. The BiTE (bispecific T-cell engager) platform: development and future potential of a targeted immuno-oncology therapy across tumor types. Cancer. 2020;126:3192–201.

    Article  CAS  PubMed  Google Scholar 

  65. Friedrich M, Raum T, Lutterbuese R, Voelkel M, Deegen P, Rau D, et al. Regression of human prostate cancer xenografts in mice by AMG 212/BAY2010112, a novel PSMA/CD3-bispecific BiTE antibody cross-reactive with non-human primate antigens. Mol Cancer Ther. 2012;11:2664–73.

    Article  CAS  PubMed  Google Scholar 

  66. Hummel H-D, Kufer P, Grüllich C, Seggewiss-Bernhardt R, Deschler-Baier B, Chatterjee M, et al. Pasotuxizumab, a BiTER immune therapy for castration-resistant prostate cancer: Phase I, dose-escalation study findings. Immunotherapy. 2021;13:125–41.

    Article  CAS  PubMed  Google Scholar 

  67. Deegen P, Thomas O, Nolan-Stevaux O, Li S, Wahl J, Bogner P, et al. The PSMA targeting half-life extended BiTE((R)) therapy AMG 160 has potent antitumor activity in preclinical models of metastatic castration-resistant prostate cancer. Clin Cancer Res. 2021;27:2928–37.

    Article  CAS  PubMed  Google Scholar 

  68. Tran B, Horvath L, Dorff T, Rettig M, Lolkema MP, Machiels JP, et al. Results from a phase I study of AMG 160, a half-life extended (HLE), PSMA-targeted, bispecific T-cell engager (BiTE®) immune therapy for metastatic castration-resistant prostate cancer (mCRPC). Ann Oncol. 2020;31:S507.

    Article  Google Scholar 

  69. Wilt TJ, Jones KM, Barry MJ, Andriole GL, Culkin D, Wheeler T, et al. Follow-up of prostatectomy versus observation for early prostate cancer. N Engl J Med. 2017;377:132–42.

    Article  PubMed  Google Scholar 

  70. Flegar L, Buerk B, Proschmann R, Propping S, Groeben C, Baunacke M, et al. Vascular-targeted photodynamic therapy in unilateral low-risk prostate cancer in Germany: 2-yr single-centre experience in a real-world setting compared with radical prostatectomy. Eur Urol Focus. 2021. https://doi.org/10.1016/j.euf.2021.01.018.

  71. Abrahamse H, Hamblin MR. New photosensitizers for photodynamic therapy. Biochem J. 2016;473:347–64.

    Article  CAS  PubMed  Google Scholar 

  72. Liu T, Wu LY, Choi JK, Berkman CE. In vitro targeted photodynamic therapy with a pyropheophorbide-a conjugated inhibitor of prostate-specific membrane antigen. Prostate. 2009;69:585–94.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  73. Liu T, Wu LY, Berkman CE. Prostate-specific membrane antigen-targeted photodynamic therapy induces rapid cytoskeletal disruption. Cancer Lett. 2010;296:106–12.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Liu T, Wu LY, Choi JK, Berkman CE. Targeted photodynamic therapy for prostate cancer: inducing apoptosis via activation of the caspase-8/-3 cascade pathway. Int J Oncol. 2010;36:777–84.

    Article  CAS  PubMed  Google Scholar 

  75. Wang X, Tsui B, Ramamurthy G, Zhang P, Meyers J, Kenney ME, et al. Theranostic agents for photodynamic therapy of prostate cancer by targeting prostate-specific membrane antigen. Mol Cancer Ther. 2016;15:1834–44.

    Article  CAS  PubMed  Google Scholar 

  76. Chen Y, Chatterjee S, Lisok A, Minn I, Pullambhatla M, Wharram B, et al. A PSMA-targeted theranostic agent for photodynamic therapy. J Photochem Photobiol B Biol. 2017;167:111–6.

    Article  CAS  Google Scholar 

  77. Overchuk M, Damen MPF, Harmatys KM, Pomper MG, Chen J, Zheng G. Long-circulating prostate-specific membrane antigen-targeted NIR phototheranostic agent. Photochem Photobiol. 2020;96:718–24.

    Article  CAS  PubMed  Google Scholar 

  78. Jilg CA, Drendel V, Rischke HC, Beck T, Vach W, Schaal K, et al. Diagnostic accuracy of Ga-68-HBED-CC-PSMA-Ligand-PET/CT before salvage lymph node dissection for recurrent prostate cancer. Theranostics. 2017;7:1770–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Horn T, Rauscher I, Eiber M, Gschwend JE, Maurer T. PSMA-radioguided surgery in localised recurrent prostate cancer. Der Urol Ausg A. 2017;56:1417–23.

    Article  CAS  Google Scholar 

  80. Schottelius M, Wirtz M, Eiber M, Maurer T, Wester HJ. [(111)In]PSMA-I&T: expanding the spectrum of PSMA-I&T applications towards SPECT and radioguided surgery. EJNMMI Res. 2015;5:68–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  81. Maurer T, Weirich G, Schottelius M, Weineisen M, Frisch B, Okur A, et al. Prostate-specific membrane antigen-radioguided surgery for metastatic lymph nodes in prostate cancer. Eur Urol. 2015;68:530–4.

    Article  PubMed  Google Scholar 

  82. Rauscher I, Duwel C, Wirtz M, Schottelius M, Wester HJ, Schwamborn K, et al. Value of (111) In-prostate-specific membrane antigen (PSMA)-radioguided surgery for salvage lymphadenectomy in recurrent prostate cancer: correlation with histopathology and clinical follow-up. BJU Int. 2017;120:40–7.

    Article  CAS  PubMed  Google Scholar 

  83. Robu S, Schottelius M, Eiber M, Maurer T, Gschwend J, Schwaiger M, et al. Preclinical evaluation and first patient application of 99mTc-PSMA-I&S for SPECT imaging and radioguided surgery in prostate cancer. J Nucl Med. 2017;58:235–42.

    Article  CAS  PubMed  Google Scholar 

  84. Maurer T, Robu S, Schottelius M, Schwamborn K, Rauscher I, van den Berg NS, et al. (99m)Technetium-based prostate-specific membrane antigen-radioguided surgery in recurrent prostate cancer. Eur Urol. 2019;75:659–66.

    Article  PubMed  Google Scholar 

  85. Knipper S, Tilki D, Mansholt J, Berliner C, Bernreuther C, Steuber T, et al. Metastases-yield and prostate-specific antigen kinetics following salvage lymph node dissection for prostate cancer: a comparison between conventional surgical approach and prostate-specific membrane antigen-radioguided surgery. Eur Urol Focus. 2019;5:50–3.

    Article  PubMed  Google Scholar 

  86. Mangano MS, De Gobbi A, Beniamin F, Lamon C, Ciaccia M, Maccatrozzo L. Robot-assisted nerve-sparing radical prostatectomy using near-infrared fluorescence technology and indocyanine green: initial experience. Urologia. 2018;85:29–31.

    Article  PubMed  Google Scholar 

  87. Wang X, Huang SS, Heston WD, Guo H, Wang BC, Basilion JP. Development of targeted near-infrared imaging agents for prostate cancer. Mol Cancer Ther. 2014;13:2595–606.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Bao K, Lee JH, Kang H, Park GK, El Fakhri G, Choi HS. PSMA-targeted contrast agents for intraoperative imaging of prostate cancer. Chem Commun. 2017;53:1611–4.

    Article  CAS  Google Scholar 

  89. Kelderhouse LE, Chelvam V, Wayua C, Mahalingam S, Poh S, Kularatne SA, et al. Development of tumor-targeted near infrared probes for fluorescence guided surgery. Bioconjugate Chem. 2013;24:1075–80.

    Article  CAS  Google Scholar 

  90. Kularatne SA, Thomas M, Myers CH, Gagare P, Kanduluru AK, Crian CJ, et al. Evaluation of novel prostate-specific membrane antigen-targeted near-infrared imaging agent for fluorescence-guided surgery of prostate cancer. Clin Cancer Res. 2019;25:177–87.

    Article  CAS  PubMed  Google Scholar 

  91. Neuman BP, Eifler JB, Castanares M, Chowdhury WH, Chen Y, Mease RC, et al. Real-time, near-infrared fluorescence imaging with an optimized dye/light source/camera combination for surgical guidance of prostate cancer. Clin Cancer Res. 2015;21:771–80.

    Article  CAS  PubMed  Google Scholar 

  92. Lütje S, Heskamp S, Franssen GM, Frielink C, Kip A, Hekman M, et al. Development and characterization of a theranostic multimodal anti-PSMA targeting agent for imaging, surgical guidance, and targeted photodynamic therapy of PSMA-expressing tumors. Theranostics. 2019;9:2924–38.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Derks YHW, Rijpkema M, Amatdjais-Groenen HIV, Kip A, Franssen GM, Sedelaar JPM, et al. Photosensitizer-based multimodal PSMA-targeting ligands for intraoperative detection of prostate cancer. Theranostics. 2021;11:1527–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  94. Wu M, Wang Y, Wang Y, Zhang M, Luo Y, Tang J, et al. Paclitaxel-loaded and A10-3.2 aptamer-targeted poly(lactide-co-glycolic acid) nanobubbles for ultrasound imaging and therapy of prostate cancer. Int J Nanomed. 2017;12:5313–30.

    Article  CAS  Google Scholar 

  95. Wu M, Zhao H, Guo L, Wang Y, Song J, Zhao X, et al. Ultrasound-mediated nanobubble destruction (UMND) facilitates the delivery of A10-3.2 aptamer targeted and siRNA-loaded cationic nanobubbles for therapy of prostate cancer. Drug Deliv. 2018;25:226–40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  96. Wang Y, Yao B, Wang Y, Zhang M, Fu S, Gao H, et al. Increased FoxM1 expression is a target for metformin in the suppression of EMT in prostate cancer. Int J Mol Med. 2014;33:1514–22.

    Article  CAS  PubMed  Google Scholar 

  97. Current K, Meyer C, Magyar CE, Mona CE, Almajano J, Slavik R, et al. Investigating PSMA-targeted radioligand therapy efficacy as a function of cellular PSMA levels and intratumoral PSMA heterogeneity. Clin Cancer Res. 2020;26:2946–55.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Paschalis A, Sheehan B, Riisnaes R, Rodrigues DN, Gurel B, Bertan C, et al. Prostate-specific membrane antigen heterogeneity and DNA repair defects in prostate cancer. Eur Urol. 2019;76:469–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  99. Farag M, Bolton D, Lawrentschuk N. Prostate-specific membrane antigen for the surgical oncologist: interpreting expression beyond the prostate. ANZ J Surg. 2020;90:715–8.

    Article  PubMed  Google Scholar 

  100. Jafari E, Ahmadzadehfar H, Dadgar H, Assadi M. An overview on prostate-specific membrane antigen uptake in malignancies other than prostate cancer: a pictorial essay. World J Nucl Med. 2020;19:260–5.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

The work is financially supported by the National Natural Science Foundation of China (81571797), the Social Development Plan of Taizhou, China (TS202004), and the Taizhou People’s Hospital Medical Innovation Team Foundation, China (CXTDA201901).

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Authors and Affiliations

  1. Nantong University, Nantong, Jiangsu, China

    Fujin Wang, Zhifeng Li, Xiaoqian Feng & Dazhuang Yang

  2. Department of Radiology, the First People’s Hospital of Yancheng, Yancheng, Jiangsu, China

    Fujin Wang & Xiaoqian Feng

  3. Taizhou People’s Hospital Affiliated to Nantong University, Taizhou, Jiangsu, China

    Mei Lin

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  1. Fujin Wang
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  2. Zhifeng Li
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  3. Xiaoqian Feng
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  4. Dazhuang Yang
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Contributions

FJW conceived and wrote the manuscript. ZFL analyzed the relevant literature. XQF created the figure and tables. DZY critically revised the manuscript. ML designed this review study and gave constructive guidance and made critical revisions.

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Correspondence to Mei Lin.

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Wang, F., Li, Z., Feng, X. et al. Advances in PSMA-targeted therapy for prostate cancer. Prostate Cancer Prostatic Dis 25, 11–26 (2022). https://doi.org/10.1038/s41391-021-00394-5

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